NM_014918.5:c.2114G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014918.5(CHSY1):c.2114G>A(p.Arg705Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,614,080 control chromosomes in the GnomAD database, including 14,703 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1082 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13621 hom. )

Consequence

CHSY1
NM_014918.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

CHSY1 (HGNC:17198): (chondroitin sulfate synthase 1) This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. These enzymes possess dual glucuronyltransferase and galactosaminyltransferase activity and play critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan involved in many biological processes including cell proliferation and morphogenesis. Decreased expression of this gene may play a role in colorectal cancer, and mutations in this gene are a cause of temtamy preaxial brachydactyly syndrome. [provided by RefSeq, Dec 2011]

CHSY1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016215444).

BP6

Variant 15-101177683-C-T is Benign according to our data. Variant chr15-101177683-C-T is described in ClinVar as [Benign]. Clinvar id is 1167689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5 link	c.2114G>A	p.Arg705Gln	missense_variant	Exon 3 of 3	ENST00000254190.4	NP_055733.2	Q86X52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHSY1	ENST00000254190.4 link	c.2114G>A	p.Arg705Gln	missense_variant	Exon 3 of 3	1	NM_014918.5	ENSP00000254190.3	Q86X52
CHSY1	ENST00000543813.2 link	n.*1429G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2		ENSP00000496160.1	A0A2R8Y7B7
CHSY1	ENST00000543813.2 link	n.*1429G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15333

AN:

152090

Hom.:

1083

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.0803

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0631

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.107

AC:

26847

AN:

251454

Hom.:

1782

AF XY:

0.109

AC XY:

14827

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0651

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0686

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.131

AC:

190848

AN:

1461872

Hom.:

13621

Cov.:

AF XY:

0.129

AC XY:

93834

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0231

Gnomad4 AMR exome

AF:

0.0663

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0689

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.101

AC:

15330

AN:

152208

Hom.:

1082

Cov.:

AF XY:

0.101

AC XY:

7522

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.0802

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0629

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.100

Alfa

AF:

0.129

Hom.:

2204

Bravo

AF:

0.0893

TwinsUK

AF:

0.156

AC:

577

ALSPAC

AF:

0.144

AC:

556

ESP6500AA

AF:

0.0275

AC:

121

ESP6500EA

AF:

0.142

AC:

1221

ExAC

AF:

0.105

AC:

12797

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

EpiCase

AF:

0.144

EpiControl

AF:

0.139

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Temtamy preaxial brachydactyly syndrome

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.026

Eigen

Benign

0.0023

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.95

REVEL

Benign

0.051

Sift

Benign

0.55

Sift4G

Benign

0.51

Polyphen

0.90

Vest4

0.042

MPC

0.37

ClinPred

0.013

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over